Palliative Care for Patients with End-Stage, Non-Oncologic Diseases-A Retrospective Study in Three Public Palliative Care Departments in Northern Italy.

Patients with irreversible malignant and non-malignant diseases have comparable mortality rates, symptom burdens, and quality of life issues; however, non-cancer patients seldom receive palliative care (PC) or receive it late in their disease trajectory. To explore the characteristics of non-cancer patients receiving PC in northern Italy, as well as the features and outcomes of their care, we retrospectively analyzed the charts of all non-cancer patients initiating PC regimens during 2019 in three publicly funded PC departments in Italy's populous Lombardy region. We recorded the baseline variables (including data collected with the NECPAL CCOMS-ICO-derived questionnaire used since 2018 to evaluate all admissions to the region's PC network), as well as treatment features (setting and duration) and outcomes (including time and setting of death). Of the 2043 patients admitted in 2019, only 12% (243 patients­131 females; mean age 83.5 years) had non-oncological primary diagnoses (mainly dementia [n = 78], heart disease [n = 55], and lung disease [n = 30]). All 243 had Karnofsky performance statuses ≤ 40% (10−20% in 64%); most (82%) were malnourished, 92% had ≥2 comorbidities, and 61% reported 2−3 severe symptoms (pain, dyspnea, and fatigue). Fifteen withdrew or were discharged from the study PCN; the other 228 remained in the PCN and died in hospice (n = 133), at home (n = 9), or after family-requested transfer to an emergency department (n = 1). Most deaths (172/228, 75%) occurred <3 weeks after PC initiation. These findings indicate that the PCN network we studied cares for few patients with life-limiting non-malignant diseases. Those admitted have advanced-stage illness, heavy symptom burdens, low performance statuses, and poor survival. Additional efforts are needed to improve PCN accessibility for non-cancer patients.

Randomized biomarker trial of anastrozole or low-dose tamoxifen or their combination in subjects with breast intraepithelial neoplasia.

PURPOSE: In the Anastrozole, Tamoxifen Alone or in Combination trial, the combination arm was inferior to anastrozole alone in terms of disease-free survival possibly due to an adverse pharmacokinetic interaction or a predominant estrogenic effect of tamoxifen under estrogen deprivation. We assessed whether the addition of a lower dose of tamoxifen influenced anastrozole bioavailability and favorably modulated biomarkers of bone fracture, breast cancer, cardiovascular disease, and endometrial cancer risk. The influence of CYP2D6 genotype on tamoxifen effects was also determined. EXPERIMENTAL DESIGN: Seventy-five postmenopausal women with breast intraepithelial neoplasia were randomly allocated to either 1 mg/d anastrozole or 10 mg/wk tamoxifen or their combination for 12 months. Study endpoints were plasma drug concentrations and changes of C-telopeptide, osteocalcin, estradiol/sex hormone binding globulin (SHBG) ratio, estrone sulfate, insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3), C-reactive protein, antithrombin-III, endometrial Ki-67 expression, and thickness. RESULTS: Anastrozole concentrations were not affected by the combination with low-dose tamoxifen, whereas endoxifen levels were lower in poor CYP2D6 metabolizers. C-telopeptide increased by 20% with anastrozole and decreased by 16% with tamoxifen and by 7% with their combination (P < 0.001); osteocalcin showed similar changes. Compared with anastrozole, the combination arm showed lower IGF-I/IGFBP-3 levels (-17% versus -9%; P = 0.004) and lower estradiol/SHBG and estrone sulfate reductions (-15% versus -29% and -30% versus 38%, respectively). However, IGF-I/IGFBP-3 and estradiol/SHBG did not decrease in poor CYP2D6 metabolizers. Endometrial thickness was not greater in the combination than in the anastrozole arm. CONCLUSIONS: The addition of a weekly tamoxifen administration did not impair anastrozole bioavailability and modulated favorably its safety profile, providing the rationale for further studies.

Complete pathological response of hepatocellular carcinoma with systemic combination chemotherapy.

Prognosis of advanced hepatocellular carcinoma is dismal when locoregional treatments have failed. Systemic chemotherapy is seldom effective in inducing objective response and prolonging survival. We report a case of complete pathological remission of hepatocellular carcinoma after three cycles of systemic chemotherapy. A 64-year-old woman presented with histologically documented hepatocellular carcinoma without associated liver disease, relapsed after earlier locoregional therapy. Surgery was not performed as thoracic computerized tomography (CT) demonstrated pulmonary bilateral nodules. The patient was treated with chemotherapy consisting of three cycles of epirubicin, cisplatin, and infusional 5-fluorouracil (ECF regimen); stable lung disease and a good partial response in the liver were obtained as documented by CT scan. Hepatic segmentectomy was therefore performed and the histologic examination revealed necrosis without evidence of residual disease. Two more cycles of adjuvant chemotherapy were infused after surgery. At 1-year follow-up the patient is alive and free of disease according to a positron emission tomography/CT scan. It is suggested that an aggressive regimen like ECF should be considered in fit patients who are not affected by concomitant liver disease.

Gemcitabine and atrial fibrillation: a rare manifestation of chemotherapy toxicity.

Gemcitabine is a purine analog with known activity in many solid tumors, namely lung, breast, pancreatic, genitourinary and head/neck cancers. Cardiac toxicity is a rare event and only one report previously described atrial fibrillation (AF) as a consequence of gemcitabine infusion. We report two cases of women suffering from lung cancer who were treated with gemcitabine. Both patients were admitted to hospital for paroxysmal AF occurring 12-24 h after the infusion of the drug. In the first case a sinus rhythm was spontaneously repristinated when AF occurred for the first time, while the second episode required an anti-arrhythmic drug to interrupt the dysrhythmia. In the second case, the patient had to be treated with digitalis glycoside to control the ventricular response without attaining a sinus rhythm. We could not recognize any other precipitating factor beyond the infusion of gemcitabine as a cause for the arrhythmia. Both cases were treated with gemcitabine for lung cancer and we observed the appearance of AF less than 24 h after drug administration. We assume that 2',2'-difluorodeoxyuridine, an active metabolite of gemcitabine, could be responsible for the toxic effect. We conclude that AF is an unusual, but potentially dangerous, side-effect of gemcitabine infusion. The arrhythmia should be suspected whenever patients complain of dyspnea and palpitations beginning 12-24 h after treatment. In these cases, the treatment of AF consists of anti-arrhythmic drugs in order to repristinate a sinus rhythm or control the heart rate.